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Cytokine biomarkers and chronic pain: association of genes, transcription, and circulating proteins with temporomandibular disorders and widespread palpation tenderness.

Publication ,  Journal Article
Slade, GD; Conrad, MS; Diatchenko, L; Rashid, NU; Zhong, S; Smith, S; Rhodes, J; Medvedev, A; Makarov, S; Maixner, W; Nackley, AG
Published in: Pain
December 2011

For reasons unknown, temporomandibular disorder (TMD) can manifest as localized pain or in conjunction with widespread pain. We evaluated relationships between cytokines and TMD without or with widespread palpation tenderness (TMD-WPT or TMD+WPT, respectively) at protein, transcription factory activity, and gene levels. Additionally, we evaluated the relationship between cytokines and intermediate phenotypes characteristic of TMD and WPT. In a case-control study of 344 females, blood samples were analyzed for levels of 22 cytokines and activity of 48 transcription factors. Intermediate phenotypes were measured by quantitative sensory testing and questionnaires asking about pain, health, and psychological status. Single nucleotide polymorphisms (SNPs) coding cytokines and transcription factors were genotyped. TMD-WPT cases had elevated protein levels of proinflammatory cytokine monocyte chemotactic protein (MCP-1) and antiinflammatory cytokine interleukin (IL)-1ra, whereas TMD+WPT cases had elevated levels of proinflammatory cytokine IL-8. MCP-1, IL-1ra, and IL-8 were differentially associated with experimental pain, self-rated pain, self-rated health, and psychological phenotypes. TMD-WPT and TMD+WPT cases had inhibited transcription activity of the antiinflammatory cytokine transforming growth factor β1 (TGFβ1). Interactions were observed between TGFβ1 and IL-8 SNPs: an additional copy of the TGFβ1 rs2241719 minor T allele was associated with twice the odds of TMD+WPT among individuals homozygous for the IL-8 rs4073 major A allele, and half the odds of TMD+WPT among individuals heterozygous for rs4073. These results demonstrate how pro- and antiinflammatory cytokines contribute to the pathophysiology of TMD and WPT in genetically susceptible people. Furthermore, they identify MCP-1, IL-1ra, IL-8, and TGFβ1 as potential diagnostic markers and therapeutic targets for pain in patients with TMD.

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Published In

Pain

DOI

EISSN

1872-6623

Publication Date

December 2011

Volume

152

Issue

12

Start / End Page

2802 / 2812

Location

United States

Related Subject Headings

  • Young Adult
  • Temporomandibular Joint Disorders
  • Surveys and Questionnaires
  • Palpation
  • Pain Measurement
  • Middle Aged
  • Humans
  • Genome-Wide Association Study
  • Female
  • Cytokines
 

Citation

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ICMJE
MLA
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Slade, G. D., Conrad, M. S., Diatchenko, L., Rashid, N. U., Zhong, S., Smith, S., … Nackley, A. G. (2011). Cytokine biomarkers and chronic pain: association of genes, transcription, and circulating proteins with temporomandibular disorders and widespread palpation tenderness. Pain, 152(12), 2802–2812. https://doi.org/10.1016/j.pain.2011.09.005
Slade, Gary D., Mathew S. Conrad, Luda Diatchenko, Naim U. Rashid, Sheng Zhong, Shad Smith, Jesse Rhodes, et al. “Cytokine biomarkers and chronic pain: association of genes, transcription, and circulating proteins with temporomandibular disorders and widespread palpation tenderness.Pain 152, no. 12 (December 2011): 2802–12. https://doi.org/10.1016/j.pain.2011.09.005.
Slade, Gary D., et al. “Cytokine biomarkers and chronic pain: association of genes, transcription, and circulating proteins with temporomandibular disorders and widespread palpation tenderness.Pain, vol. 152, no. 12, Dec. 2011, pp. 2802–12. Pubmed, doi:10.1016/j.pain.2011.09.005.
Slade GD, Conrad MS, Diatchenko L, Rashid NU, Zhong S, Smith S, Rhodes J, Medvedev A, Makarov S, Maixner W, Nackley AG. Cytokine biomarkers and chronic pain: association of genes, transcription, and circulating proteins with temporomandibular disorders and widespread palpation tenderness. Pain. 2011 Dec;152(12):2802–2812.

Published In

Pain

DOI

EISSN

1872-6623

Publication Date

December 2011

Volume

152

Issue

12

Start / End Page

2802 / 2812

Location

United States

Related Subject Headings

  • Young Adult
  • Temporomandibular Joint Disorders
  • Surveys and Questionnaires
  • Palpation
  • Pain Measurement
  • Middle Aged
  • Humans
  • Genome-Wide Association Study
  • Female
  • Cytokines